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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
1
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pubmed:dateCreated |
2009-3-13
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pubmed:abstractText |
Salt inducible kinase (SIK) 1, a member of the AMP-activated kinase (AMPK) family, is activated by the AMPK-activator LKB1 which phosphorylates SIK1 at Thr182. The activated SIK1 then auto-phosphorylates its Ser186 located at the +4 position of Thr182. The phospho-Ser186 is essential for sustained activity of SIK1, which is maintained by sequential phosphorylation at Ser186-Thr182 by glycogen synthase kinase (GSK)-3beta. Meanwhile, SIK1 represses the transcription factor cAMP-response element binding protein (CREB) by phosphorylating its co-activator transducer of regulated CREB activity (TORC). Recently, histone deacetylase (HDAC) 5 was identified as a new substrate of SIK1. Inhibition of SIK1 or AMPK results in the stimulation of glyconeogensis in the liver by enhancing dephosphorylation of TORC2 followed by up-regulation of peroxisome proliferator-activated receptor coactivator (PGC)-1alpha gene expression. However, expression of the PGC-1alpha gene has been found to be repressed in LKB1-defective muscle cells. Our findings show that the AMPK agonist 5-aminoimidazole-4-carboxamide-1-beta-d-ribofuranoside (AICAR)-dependent expression of PGC-1alpha is diminished by inhibitors of GSK-3beta or SIKs in C2C12 myoblasts. Treatment with AICAR or the overexpression of SIK1 induces nuclear export of HDAC5 followed by the activation of myogenic transcription factor (MEF)-2C. The levels of phosphorylation at Thr182 and Ser186 of SIK1 in AICAR-treated C2C12 cells are elevated, and GSK-3beta enzyme purified from AICAR-treated cells shows enhanced phosphorylation activity of SIK1 in vitro. These observations suggest that GSK-3 beta and SIK1 may play important roles in the regulation of PGC-1alpha gene expression by inactivating HDAC5 followed by activation of MEF2C.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/AICA ribonucleotide,
http://linkedlifedata.com/resource/pubmed/chemical/Aminoimidazole Carboxamide,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Glycogen Synthase Kinase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Hdac5 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Histone Deacetylase Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Histone Deacetylases,
http://linkedlifedata.com/resource/pubmed/chemical/Mef2c protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Myogenic Regulatory Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Ppargc1a protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Ribonucleotides,
http://linkedlifedata.com/resource/pubmed/chemical/Serine,
http://linkedlifedata.com/resource/pubmed/chemical/Sik1 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Threonine,
http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators,
http://linkedlifedata.com/resource/pubmed/chemical/glycogen synthase kinase 3 beta
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pubmed:status |
MEDLINE
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pubmed:issn |
1348-4540
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:volume |
56
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
121-30
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pubmed:dateRevised |
2011-11-2
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pubmed:meshHeading |
pubmed-meshheading:18946175-Aminoimidazole Carboxamide,
pubmed-meshheading:18946175-Animals,
pubmed-meshheading:18946175-Cell Line,
pubmed-meshheading:18946175-Enzyme Activation,
pubmed-meshheading:18946175-Enzyme Inhibitors,
pubmed-meshheading:18946175-Gene Expression Regulation,
pubmed-meshheading:18946175-Glycogen Synthase Kinase 3,
pubmed-meshheading:18946175-Histone Deacetylase Inhibitors,
pubmed-meshheading:18946175-Histone Deacetylases,
pubmed-meshheading:18946175-Mice,
pubmed-meshheading:18946175-Myoblasts,
pubmed-meshheading:18946175-Myogenic Regulatory Factors,
pubmed-meshheading:18946175-Phosphorylation,
pubmed-meshheading:18946175-Protein-Serine-Threonine Kinases,
pubmed-meshheading:18946175-Rats,
pubmed-meshheading:18946175-Ribonucleotides,
pubmed-meshheading:18946175-Serine,
pubmed-meshheading:18946175-Signal Transduction,
pubmed-meshheading:18946175-Threonine,
pubmed-meshheading:18946175-Trans-Activators
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pubmed:year |
2009
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pubmed:articleTitle |
Inactivation of HDAC5 by SIK1 in AICAR-treated C2C12 myoblasts.
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pubmed:affiliation |
Laboratory of Cell Signaling and Metabolism, National Institute of Biomedical Innovation, Osaka, Japan.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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